1. Field of the Invention
This invention is generally directed to chemical and biochemical analysis of an analyte in a fluid or gaseous mixture, and more specifically relates to methods of stabilizing measurements taken with an intravascular carbon dioxide sensor.
2. Description of Related Art
Measurement of acidity (pH) and the tension or partial pressure of carbon dioxide and oxygen in the blood have become important in modern medicine, particularly with regard to determining the respiratory condition of a patient. Although electrodes have been developed which are capable of making such measurements, they are generally of limited use in the medical field. Optical sensors for taking intravascular measurements of acidity, carbon dioxide and oxygen levels in the blood have also been developed, based upon the principle of enclosing a fluorescent indicator within a membrane permeable to the analyte to be measured, coupled to one or more optical fibers for measuring the intensity of fluorescence from the indicator. Since the fluorescence reaction of appropriately chosen indicators is altered according to the level of acidity, carbon dioxide, or oxygen being measured, these sensors allow remote measurement of these parameters when combined with compatible intravascular catheter systems.
A fiber optic chemical sensor may also be used for measuring pH by the use of optical absorbance indicators, such as phenol red, which may be chemically bound in the sensor. In this type of pH sensor, green and red light typically emerge from one optical fiber into the sensor, passing through the dye, to be reflected back through an optical fiber to a detector system. The green light is absorbed by the base form of the indicator, and the red light is not absorbed by the indicator, so that the red light may be used as an optical reference. The ratio of green to red light can then be measured, and related to pH.
A fluorescent indicator may be used in a similar fashion, with light in one wavelength region being used to excite the fluorescent indicator dye to emit light of a different wavelength. Such optical pH sensors typically include a fluorescent indicator dye, such as fluorescein or hydroxypyrenetrisulfonic acid (HPTS), placed over the tip of an optical fiber and a membrane cover over the dye which is permeable to the hydronium ions to be measured. The dye fluoresces when exposed to a certain wavelength of light conducted to it by the optical fiber. In practice, a pH sensor is fabricated by immobilizing a pH sensitive dye into a matrix attached to the distal end of the fiber. The dye . is typically capable of existing in two forms, an anionic or base form, and a protonated or acid form. The two forms are each excited by a different frequency, but fluoresce at the same frequency, with the output responsive to excitation at the appropriate different frequencies being proportional to the pH of the sample to which the sensor is exposed. In this manner, measurement of the intensity of fluorescence of the indicator dye can be related to pH. A clinically useful range for measuring carbon dioxide as a blood gas parameter has been found to be from about 1.4 weight percent to about 15 weight percent carbon dioxide. Therefore, it is desirable for a carbon dioxide sensor to be accurate and repeatable over at least this range.
It has also been found that carbon dioxide sensors frequently become destabilized when exposed to low carbon dioxide levels, and that a progressive loss of fluorescent intensity occurs in sensors utilizing fluorescent indicators after exposure to high carbon dioxide concentrations. The instability of such fiber optic based carbon dioxide sensors when the sensors are exposed to either very low or very high carbon dioxide levels for prolonged periods of time, such as several days, frequently results in non-specific drift of measurements of carbon dioxide levels. It would therefore be desirable to provide a carbon dioxide blood gas sensor which mitigates this non-specific drift instability.